Immunohistochemical study on distribution of NF-kappaB and p53 in gerbil hippocampus after transient cerebral ischemia: effect of pitavastatin

• Published in: Metabolic brain disease Vol. 22; no. 1; pp. 89 - 104
• Main Authors: Tounai, Hiroko, Hayakawa, Natsumi, Kato, Hiroyuki, Araki, Tsutomu
• Format: Journal Article
• Language: English
• Published: United States 01.03.2007
• Subjects: Animals; Apoptosis - drug effects; Astrocytes - metabolism; Astrocytes - pathology; Enzyme Inhibitors - pharmacology; Gerbillinae; Hippocampus - metabolism; Hippocampus - pathology; Immunohistochemistry; Ischemic Attack, Transient - drug therapy; Ischemic Attack, Transient - metabolism; Ischemic Attack, Transient - pathology; Male; Microglia - metabolism; Microglia - pathology; Nerve Tissue Proteins - metabolism; Oxidative Stress - drug effects; Quinolines - pharmacology; Transcription Factor RelA - metabolism; Tumor Suppressor Protein p53 - metabolism
• ISSN: 0885-7490

We investigated the immunohistochemical alterations of the transcription nuclear factor kappa-B (NF-kappaB) and transcription factor p53 in the hippocampus after transient cerebral ischemia in gerbils. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin against the alterations of NF-kappaB, p53 and neuronal nuclei in the hippocampus after ischemia. Severe neuronal damage was observed in the hippocampal CA1 neurons 5 and 14 days after ischemia. In the present study, the increase of NF-kappaB immunoreactivity in glial cells and p53 immunoreactivity in neurons preceded neuronal damage in the hippocampal CA1 sector after ischemia. Thereafter, NF-kappaB immunoreactivity was induced highly in reactive astrocytes and microglia of the hippocampal CA1 sector where severe neuronal damage was observed. Our immunohistochemical study showed that pitavastatin prevented the alterations of NF-kappaB and p53 in the hippocampal CA1 sector 5 days after transient ischemia. Furthermore, our results with neuronal nuclei immunostaining indicate that pitavastatin dose-dependently prevented the neuronal cell death in the hippocampal CA1 sector 5 days after transient cerebral ischemia. These results suggest that the up-regulations of NF-kappaB in glia and p53 in neurons can cause neuronal cell death after ischemia. Our findings also support the hypothesis that NF-kappaB- and/or p53-mediated neuronal cell death is prevented through decreasing oxidative stress by pitavastatin. Thus, NF-kappaB and p53 may provide an attractive target for the development of novel therapeutic approaches for brain stroke.